Our long-term research goal is to develop implantable neurotechnologies for long-term and high fidelity microscale electrical and chemical interfaces to the central nervous system. The objective of this two-year project is to develop a new type of multi-modal neural probe by integrating chemical sensors on microfabricated thin-film silicon devices that are presently used for neural recording, stimulation, and microscale drug injection. The first specific aim is to develop and characterize integrated chemical sensing of two electroactive neurochemicals (dopamine and serotonin), along with concurrent electrophysiological recording. The primary tasks include developing electrode site materials, integrating a reference electrode onto the probe substrate, and characterizing 'electrode site spacing for concurrent neurochemical sensing and electrophysiological recording. The second specific aim is to develop arid characterize integrated chemical sensing of two non-electroactive neurochemicals (acetylcholine and glutamate), along with concurrent electrophysiological recording and microfluidic delivery of pharmacological agents. The primary tasks of this aim include developing polymer wells and conductive polymer coatings for enzyme entrapment and characterizing sensor performance. In both aims, the multi-modal devices will be quantitatively evaluated and systematically refined through bench top testing and in vivo acute experiments. This project significantly extends the state-of-the-art for microscale neural interfaces by developing a new technology that combines precise, high-resolution neurochemical sensing with high-fidelity neural recording and targeted drug delivery. This technology is likely to provide a solid foundation for developing a new class of implantable device that will enable next-generation, closed-loop neuroprostheses and neuromodulation systems for improved treatments of neurological disease and injury, such as Parkinson's Disease and severe movement disorders.